Preoperative, Proton- Radiotherapy Combined With Chemotherapy for Borderline Resectable Pancreatic Cancer

Overview

This is an interventional, single arm, open-label, feasibility trial with gemcitabine and nab-paclitaxel, followed by concomitant proton therapy and capecitabine, followed by re-evaluation and surgery (when feasible) for patients with borderline resectable pancreatic cancer.

Detailed description

This is an interventional, single arm, open label, feasibility trial of preoperative chemotherapy + concomitant chemo-proton therapy followed by surgery (when feasible) for patients with borderline resectable pancreatic cancer. Aim of this study is to test referral and enrollment procedures as well as technical feasibility. Proton therapy will be delivered in MedAustron, which is a stand alone facility. Pancreatic cancer patients are typically complex cases that require multidisciplinary care. Moreover delivery of high dose of proton therapy to large volumes including the upper abdomen lymphnodes and pancreatic neural plexus is technically challenging, therefore a feasibility study is deemed necessary. Following this study, a larger study will be performed aiming to confirm the ability of preoperative chemotherapy + concomitant chemo-proton therapy to improve resectability and ultimately outcome of borderline resectable pancreatic cancer without increase in toxicity.

Interventions

• Radiation Proton Ions
  According to the radiation plan (between 50.4 and a maximum of 60.2 Gy) after Chemotherapy with Nab-PACLitaxel (Abraxane®) + Gemcitabine and concomitant to Capecitabine.
• Drug Nab-PACLitaxel
  Chemotherapy will be delivered upfront for three cycles (week 2-4, week 6-8 and week 10-12) with combined Nab-PACLitaxel (Abraxane®) and Gemcitabine Therapy. It will be administered as intra venous infusion over 30 minutes.
• Drug Gemcitabine
  Chemotherapy will be delivered upfront for three cycles (week 2-4, week 6-8 and week 10-12) with combined Nab-PACLitaxel (Abraxane®) and Gemcitabine Therapy. Gemcitabine will also be administered as intra venous infusion over 30 minutes immediately after Nab-PACLitaxel.
• Drug Capecitabine
  Concomitant to proton-radiotherapy (on the same days, within week 14-19)
• Procedure Surgical resection of the pancreas (when feasible)
  Pre surgical re-evaluation will be performed at week 21 after enrollment. Patients fulfilling surgery-entry criteria, which consist of no distant metastasis, no massive ascites, no massive pleural effusion, no serious infection, no serious, unresolved chemoradiotherapy related, adverse events and adequate organ system function, will undergo surgery on week 22 (± 1 week). This should be performed via laparotomy.

Primary outcome measures

• Toxicity - Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [Time frame: from enrollment to six months after surgery]
• Perioperative Mortality and Complications [Time frame: 90 days postoperatively]

Secondary outcome measures (9)

• Toxicity - CTCAE v5.0 [Time frame: from enrollment to six months after surgery]
• Tumor recurrence [Time frame: 260 weeks after therapy]
• Progression free survival [Time frame: 260 weeks after therapy]
• Overall survival [Time frame: 282 weeks]
• Pathologic tumor response [Time frame: 260 weeks]
• Radiologic response [Time frame: 263 weeks after proton therapy]
• Quality of Life questionnaire: Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) [Time frame: 282 weeks]
• Quality of Life questionnaire: European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-30) [Time frame: 282 weeks]
• Quality of Life questionnaire: Brief Pain Inventory [Time frame: 282 weeks]

Eligibility criteria

Inclusion criteria

• Patients with histologically or cytologically confirmed diagnosis of pancreatic cancer
• Diagnosis of borderline resectable cancer according to the international consensus definition 2017.
• Negative staging for distant metastasis
• Blood test within the following limits absolute neutrophil count > 1,500 cells/mm³, platelet count > 100,000 cells/mm³, Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) < 2.5 times the upper limit of normal, total bilirubin < 2.5 times the upper limit of normal if patient had recent biliary stenting, total bilirubin < 1.5 times the upper limit of normal if no biliary stenting was done, serum creatinine within normal range (0.6-1.5 mg/dl) with a creatinine clearance > 30 ml/min (as estimated by Cockroft Gault equation)
• Age > 18 years
• Karnofsky index ≥ 70
• No tumor infiltration of stomach or duodenum
• The patient is informed of the diagnosis and is able to give informed consent (Ability of subject to understand character and individual consequences of the study protocol)
• Women of fertile age must have adequate conception prevention measures and must not breast feed
• Signed Informed Consent (must be available before study inclusion)

Exclusion criteria

• Non-exocrine tumors
• Major medical or psychiatric comorbidities that contraindicate radiation therapy, chemotherapy or surgery
• Presence of distant metastasis
• Pregnancy or unwilling to do adequate conception prevention
• Lactating and unwilling to discontinue lactation
• Men of childbearing potential not willing to use effective means of contraception
• Known allergic/hypersensitivity reaction to any of the components of study treatments
• Previous diagnosis of another neoplasm with worse prognosis as compared with the one in this study
• Metallic prosthesis or other condition that prevent an adequate imaging for target volume definition
• Loco-regional conditions that contraindicate radiotherapy e.g. active infections in the area
• Previous abdominal radiotherapy
• Prior systemic treatment for pancreatic cancer
• Hypersensitivity to PACLitaxel, albumin, gemcitabine or to any of the excipients of the chemotherapy
• Severe hepatic impairment
• Baseline Neutrophil Counts < 1.5 x 10\^9/L
• Baseline Grade ≥ 2 sensory or motor neuropathy
• Patient refusal

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

Austria · 2 centers

• EBG MedAustron GmbH — Wiener Neustadt
• Department of Surgery, LK Wiener Neustadt — Wiener Neustadt

Identifiers

NCT: NCT04894643 · PARC-MA-062019

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗